Rapidly disintegrating tablet comprising an acid-labile active ingredient

ABSTRACT

A rapidly disintegrating tablet for oral administration of acid-labile active ingredients is described. The rapidly disintegrating tablet for oral administration of an acid-labile active ingredient comprises a plurality of individual active ingredient units together with pharmaceutical excipients, where the acid-labile active ingredient is present in the individual active ingredient units in a matrix composed of a mixture comprising at least one solid paraffin and one or more substances from the group of fatty alcohol, triglyceride and fatty acid ester, and where excipients which, on oral intake of the tablet, bring about rapid disintegration of the tablet are present.

TECHNICAL FIELD

The present invention relates to the field of pharmaceutical technologyand describes a rapidly disintegrating tablet comprising an acid-labileactive ingredient, in particular an acid-labile proton pump inhibitor.The invention also relates to processes for producing the tablet.

BACKGROUND ART

It is generally known to coat oral dosage forms, e.g. tablets orpellets, which comprise an acid-labile active ingredient, with anenteric coating which, after passing through the stomach, rapidlydissolves in the alkaline medium in the intestine. One example of suchacid-labile active ingredients comprises acid-labile proton pumpinhibitors (H⁺/K⁺-ATPase inhibitors), in particularpyridin-2-ylmethylsulfinyl-1H-benzimidazoles like those disclosed, forexample, in EP-A-0 005 129, EP-A-0 166 287, EP-A-0 174 726 and EP-A-0268 956. Because of their H⁺/K⁺-ATPase-inhibiting effect, they areimportant in the therapy of disorders originating from increased gastricacid secretion. Examples of active ingredients from this group which arealready commercially available are5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]-1H-benzimidazole(INN: omeprazole),5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyl]-1H-benzimidazole(INN: pantoprazole),2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methylsulfinyl]-1H-benzimidazole(INN: lansoprazole) and2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl}-1H-benzimidazole(INN: rabeprazole).

Because of their great tendency to decompose in a neutral and, inparticular, acidic environment, with production also of highly coloreddecomposition products, it is also necessary in this case for oralpreparations to protect active ingredients from the effect of acids.With the very acid-labile pyridin-2-ylmethylsulfinyl-1H-benzimidazolesit is additionally necessary for them to be processed in the tablet coreor in pellets in the form of their alkaline salts, for example as sodiumsalts, or together with alkaline substances. Since substances suitablefor enteric coatings are those with free carboxyl groups, the problemarises that the enteric coating is, because of the alkaline medium inthe interior, partially or even completely dissolved from inside, andthe free carboxyl groups promote decomposition of the active ingredient.It is therefore necessary to provide a sealing intermediate layer(subcoating) between the enteric coating and the alkaline tablet core orpellet. EP-A-0 244 380 proposes that cores which contain the activeingredient together with alkaline compounds or as alkaline salt becoated with at least one layer which is soluble in water or rapidlydisintegrates in water and is composed of nonacidic, inertpharmaceutically acceptable substances, before the enteric layer isapplied. The intermediate layer or intermediate layers act aspH-buffering zones in which hydrogen ions diffusing in from outside areable to react with the hydroxyl ions diffusing out of the alkaline core.In order to increase the buffer capacity of the intermediate layer, itis proposed to incorporate buffer substances into the intermediatelayer(s). By this process it is possible in practice to obtainreasonably stable preparations. However, relatively thick intermediatelayers are required in order to avoid the unsightly discolorations whichoccur even with only slight decomposition. In addition, considerableeffort must be invested to avoid traces of moisture during production.

WO96/01623, WO96/01624 and WO96/01625 describe a dosage form foracid-labile H⁺/K⁺-ATPase inhibitors where the active ingredient unitsare compressed together with tablet excipients to give a tablet. Theactive ingredient units consist of cores which contain the acid-labileH⁺/K⁺-APTase inhibitor together with alkaline compounds or as alkalinesalt. The cores of the active ingredient units are coated with one ormore layers, and at least one layer has enteric properties. The entericlayer must in this case have mechanical characteristics such that theacid resistance of the active ingredient units is not impaired oncompression to tablets. WO97/25030 describes the processing of theaforementioned active ingredient units to a multiparticulate (multipleunit) effervescent tablet. In this case too it is necessary for theenteric layer to have mechanical characteristics such that the acidresistance of the active ingredient units is not impaired on compressionof the active ingredient units with the other ingredients of theeffervescent tablet.

EP 0 548 356 describes a rapidly disintegrating multiparticulate tabletform where the active ingredient is in the form of coated microcrystalsor coated microgranules. This rapidly disintegrating tablet form is saidto have the advantage that it can be taken by the patient very simplyand anywhere, because it can be taken without water. In addition, thisform is said to have advantages for patients who have difficulties withswallowing, such as, for example, elderly people and small children. Itwould be desirable to provide acid-labile active ingredients likewise insuch a form. As the aforementioned background art shows, however, theproduction of dosage forms such as tablets for acid-labile activeingredients, in particular for acid-labile proton pump inhibitors,requires technically complicated processes because it is necessary, forexample, to avoid the acid resistance of the active ingredient unitsbeing impaired on compression of the active ingredient with the tabletexcipients.

DESCRIPTION OF THE INVENTION

It is an object of the present invention to provide a rapidlydisintegrating dosage form for the oral administration of acid-labileactive ingredients which can be produced without great technicalcomplexity, is stable and displays good controllability of activeingredient delivery. Another object of the invention is to provide arapidly disintegrating dosage form in which it is unnecessary to protectan acid-labile active ingredient by an enteric coating.

It has now been found, surprisingly, that this object can be achieved bya rapidly disintegrating tablet comprising a plurality of individualactive ingredient units together with one or more pharmaceuticalexcipients, where the acid-labile active ingredient is present in theindividual active ingredient units in a matrix composed of a mixturecomprising at least one solid paraffin and one or more substances fromthe group of fatty alcohol, triglyceride and fatty acid ester, and wherepharmaceutical excipients which, on oral intake of the tablet, bringabout rapid disintegration of the tablet are present.

The invention therefore relates to a rapidly disintegrating tablet fororal administration of an acid-labile active ingredient comprising aplurality of individual active ingredient units together with one ormore pharmaceutical excipients, where the acid-labile active ingredientis present in the individual active ingredient units in a matrixcomposed of a mixture comprising at least one solid paraffin and one ormore substances from the group of fatty alcohol, triglyceride and fattyacid ester, and where excipients which, on oral intake of the tablet,bring about rapid disintegration of the tablet are present.

The invention further relates to a rapidly disintegrating tablet fororal administration of an acid-labile active ingredient comprising aplurality of individual active ingredient units together with one ormore pharmaceutical excipients, where the acid-labile active ingredientis present in the individual active ingredient units i) in a matrixcomposed of a mixture comprising at least one fatty alcohol and at leastone solid paraffin, ii) in a matrix composed of a mixture comprising atleast one triglyceride and at least one solid paraffin or iii) in amatrix composed of a mixture comprising at least one fatty acid esterand at least one solid paraffin, and where excipients which, on oralintake of the tablet, bring about rapid disintegration of the tablet arepresent.

Further subject matters are evident from the claims.

The numerous individual active ingredient units (also referred tohereinafter as preparations) for the purposes of the invention comprisenumerous individual units in which at least one active ingredientparticle, preferably a plurality of active ingredient particles, ispresent in a matrix composed of a mixture comprising at least one solidparaffin and one or more substances from the group of fatty alcohol,triglyceride and fatty acid ester. A plurality of active ingredientparticles is preferably present i) in a matrix composed of a mixturecomprising at least one fatty alcohol and at least one solid paraffin,ii) in a matrix composed of a mixture of at least one triglyceride andat least one solid paraffin or iii) in a matrix composed of a mixture ofat least one fatty acid ester and at least one solid paraffin. Theactive ingredient is preferably present in essentially uniformdistribution, in particular in the homogeneous dispersion or solution,in the matrix. The active ingredient units are preferably microspheres.

The active ingredient units of the invention are distinguished inparticular by high stability, an active ingredient release which can becontrolled via the particle size and composition of the matrix, goodflow characteristics, good compressibility and a uniform delivery ofactive ingredient. It is particularly worthy of mention that the activeingredient units of the invention can be further processed to a largenumber of pharmaceutical dosage forms without thereby losing a givenfunctionality (such as taste masking, resistance to gastric juice,slowing of release). Thus, for example, on compression of the activeingredient units of the invention, no loss of functionality is observedeven if there is deformation of the active ingredient units, whichoccurs in some circumstances. In contrast to this, with conventionalpellets having a functional coating (such as taste masking, resistanceto gastric juice, slowing of release) there is observed to be on furtherprocessing to dosage forms, for example on compression to tablets, acertain degree of damage to the coating and thus to the functionality.This may also lead to unwanted release of active ingredient in somecases.

The particle size of the individual units is advantageously less than orequal to 2 mm, preferably 50–800 μm, particularly preferably 50–700 μmand very particularly preferably 50–600 μm. Microspheres with a particlesize of 50–500 μm, particularly preferably of 50–400 μm, are preferred.Monomodal microspheres with a particle size of 50–400 μm, particularlypreferably of 50–200 μm, are particularly preferred.

Examples of acid-labile active ingredients in the sense of the presentinvention are acid-labile proton pump inhibitors.

Acid-labile proton pump inhibitors (H⁺/K⁺-APTase inhibitors) in thesense of the present invention which should be particularly mentionedare substituted pyridin-2-ylmethylsulfinyl-1H-benzimidazoles like thosedisclosed, for example, in EP-A-0 005 129, EP-A-0 166 287, EP-A-0 174726, EP-A-0 184 322, EP-A-0 261 478 and EP-A-0 268 956. Those which maybe mentioned as preferred in this connection are5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl)-1H-benzimidazole(INN: omeprazole),5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)methylsulfinyl]-1H-benzimidazole(INN: pantoprazole),2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methylsulfinyl)-1H-benzimidazole(INN: lansoprazole) and2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzimidazole(INN: rabeprazole).

Further acid-labile proton pump inhibitors, for example substitutedphenylmethylsulfinyl-1H-benzimidazoles,cycloheptapyridin-9-ylsulfinyl-1H-benzimidazoles orpyridin-2-ylmethylsulfinylthienoimidazoles are disclosed in DE-A 35 31487, EP-A-0 434 999 and EP-A-0 234 485. Examples which may be mentionedare 2-[2-(N-isobutyl-N-methylamino)benzylsulfinyl]benzimidazole (INN:leminoprazole) and2-(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylsulfinyl)-1H-benzimidazol(INN: nepaprazole).

The acid-labile proton pump inhibitors are chiral compounds. The term“acid-labile proton pump inhibitor” also encompasses the pureenantiomers of the acid-labile proton pump inhibitors and their mixturesin any mixing ratio. Pure enantiomers which may be mentioned by way ofexample are5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole(INN: esome prazole) and (−)-pantoprazole.

The acid-labile proton pump inhibitors are moreover present as such or,preferably, in the form of their salts with bases. Examples of saltswith bases which may be mentioned are sodium, potassium, magnesium orcalcium salts. If the acid-labile proton pump inhibitors are isolated incrystalline form, they may contain variable amounts of solvent. The termacid-labile proton pump inhibitor therefore also represents according tothe invention all solvates, in particular all hydrates, of theacid-labile proton pump inhibitors and their salts. Such a hydrate ofthe salt of an acid-labile proton pump inhibitor with a base isdisclosed, for example, in WO91/19710.

Acid-labile proton pump inhibitors which may be mentioned asparticularly preferred are pantoprazole sodium sesquihydrate(=pantoprazole sodium×1.5 H₂O), (−)-pantoprazole sodium sesquihydrate,Pantoprazole magnesium dehydrate, omeprazole magnesium, omeprazole andesomeprazole.

The fatty alcohol is preferably a linear, saturated or unsaturatedprimary alcohol with 10–30 carbon atoms. It is preferably a primaryalcohol with 10 to 18 carbon atoms in linear chains. Examples of fattyalcohols which may be mentioned are cetyl alcohol, myristyl alcohol,lauryl alcohol or stearyl alcohol, with preference for cetyl alcohol. Itis also possible if desired for mixtures of fatty alcohols to bepresent.

The triglyceride is glycerol with its three hydroxyl groups esterifiedby carboxylic acids. The carboxylic acids are preferably monobasiccarboxylic acids with 8 to 22 carbon atoms, preferably naturallyoccurring carboxylic acids. It is possible in this case for thecarboxylic acids to be different or, preferably, identical. Exampleswhich may be mentioned are tristearate, tripalmitate and, particularlypreferably, trimyristate (these triglycerides are commercially availableunder the name Dynasan 118, 116 and 114 respectively). It is alsopossible if desired for mixtures of triglycerides to be present.

The fatty acid ester is the ester of an alcohol with a fatty acid. Thealcohol in this case is preferably a linear, saturated or unsaturatedprimary alcohol with 10–30, preferably with 12 to 18, carbon atoms. Thefatty acid is preferably a monobasic carboxylic acid with 8 to 22, inparticular 12 to 18, carbon atoms, preferably a naturally occurringcarboxylic acid. Fatty acid esters preferred according to the inventionhave a melting point above 30° C. Examples of fatty acid esters whichmay be mentioned are cetyl palmitate, which is commercially availablefor example under the name Cutina® CP. It is also possible if desiredfor mixtures of fatty acid esters to be present.

The solid paraffin is preferably paraffinum solidum (ceresin). It isalso possible alternatively to use ozokerite, for example. It is alsopossible if desired to use mixtures.

If desired, the mixtures in the individual active ingredient units mayinclude one or more other pharmaceutically suitable excipients. Othersuitable excipients which may be mentioned by way of example arepolymers, sterols and basic compounds.

Examples of polymers which may be mentioned are povidone (e.g. Kollidon®17, 30 and 90 from BASF), vinylpyrrolidone/vinyl acetate copolymer andpolyvinyl acetate. Others which may be mentioned are cellulose ethers[such as, for example, methylcellulose, ethylcellulose (Ethocel®) andhydroxypropylmethylcellulose], cellulose esters [such as celluloseacetate phthalate (CAP), cellulose acetate trimellitate (CAT),hydroxypropylmethylcellulose phthalate (HP50 and HP55) orhydroxypropylmethylcellulose acetate succinate (HPMCAS)], methacrylicacid/methyl methacrylate copolymer or methacrylic acid/ethylmethacrylate copolymer (Eudragit® L). The polymer is preferably povidoneor ethylcellulose. It is also possible if desired for mixtures ofpolymers to be present. It is possible by adding suitable polymers, forexample, to influence the pharmaceutical properties of the individualactive ingredient units (e.g. delivery of the active ingredient).

The sterol is preferably a phytosterol or a zoosterol. Examples ofphytosterols which may be mentioned are ergosterol, stigmasterol,sitosterol, brassicasterol and campesterol. Examples of zoosterols whichmay be mentioned are cholesterol and lanosterol. It is also possible ifdesired for mixtures of sterols to be present.

Examples of suitable basic compounds are inorganic basic salts such asammonium carbonate and sodium carbonate, amines such as meglumine, di-,triethylamine and TRIS(2-amino-2-hydroxymethyl-1,3-propanediol) or fattyamines such as stearylamine. Stearylamine may be mentioned as preferred.The addition of basic compounds to the mixtures in the individual unitsresults in particularly stable preparations and prevents possiblediscolorations.

The proportion (in percent by weight) of active ingredient in theindividual active ingredient unit is advantageously 1–90%. Theproportion of active ingredient is preferably 2–70%, particularlypreferably 5–40%, in particular 10–20%. The proportion of fatty alcoholin the individual active ingredient unit is advantageously 10–70%,preferably 20–70%, particularly preferably 20–60% and in particular30–60% The proportion of triglyceride in the individual activeingredient unit is advantageously 10–70%, preferably 20–70%,particularly preferably 20–60% and in particular 30–60%. The proportionof fatty acid ester in the individual active ingredient unit isadvantageously 10–70%, preferably 20–70%, particularly preferably 20–60%and in particular 30–60%. The proportion of solid paraffin isadvantageously 10–70%, preferably 20–60% and in particular 30–60%. Ifpresent, the proportion of polymer in the individual active ingredientunit is expediently 1–25%, preferably 1–10%, particularly preferably5–10%. If present, the proportion of sterol is expediently 1–10%,preferably 1–5%. If present, the proportion of basic compound is0.05–5%, preferably 0.1–1%.

Preferred individual active ingredient units of the invention consist of2–70% active ingredient, 10–60% fatty alcohol, 10–60% solid paraffin,1–15% polymer and 0.1–2% of a basic compound. Further particularlypreferred individual active ingredient units of the invention consist of2–70% active ingredient, 10–60% triglyceride, 10–60% solid paraffin,1–15% polymer and 0.1–2% of a basic compound. Other particularlypreferred individual active ingredient units of the invention consist of2–70% active ingredient, 10–60% fatty acid ester, 10–60% solid paraffin,1–15% polymer and 0.1–2% of a basic compound.

Particularly preferred individual active ingredient units of theinvention consist of 5–40% active ingredient, 20–60% fatty alcohol,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.Further particularly preferred individual active ingredient units of theinvention consist of 5–40% active ingredient, 20–60% triglyceride,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.Other particularly preferred individual active ingredient units of theinvention consist of 5–40% active ingredient, 20–60% fatty acid ester,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.

Examples of active ingredient units of the invention contain 5–40%pantoprazole sodium sesquihydrate, 10–40% cetyl alcohol, 5–60% solidparaffin, 1–5% polymer and 0.1–0.2% of a basic compound. Furtherexamples of active ingredient units of the invention contain 5–40%pantoprazole sodium sesquihydrate, 10–40% glyceryl tripalmitate, 5–60%solid paraffin, 1–5% polymer and 0.1–0.2% of a basic compound. Otherexamples of active ingredient units of the invention contain 5–40%pantoprazole sodium sesquihydrate, 10–40% glyceryl tripalmitate, 5–60%solid paraffin, 1–5% polymer and 0.1–0.2% of a basic compound. Stillother examples of active ingredient units of the invention contain10–20% pantoprazole sodium sesquihydrate, 20–40% triglyceride, 40–70%solid paraffin, 1–5% sterol and 0.05–0.1% of a basic compound.

The individual active ingredient units can be produced for example byspray drying or, preferably, by spray solidification, in particular alsoby spray prilling. Production is particularly preferably by prilling, inparticular by vibration prilling.

For the spray solidification or prilling expediently the fatty alcohol,the triglyceride and/or the fatty acid ester is liquefied together withthe solid paraffin and, if desired, other excipients to give a clearmelt. The active ingredient is dissolved or dispersed in this solution,and the resulting solution or dispersion is sprayed or, preferably,prilled in a suitable apparatus. A dispersion of the active ingredientin a melt of the excipients is preferably used.

Spray solidification takes place in a manner known per se. A detaileddescription of this technique is to be found in P. B. Deasy,Microencapsulation and Related Drug Processes (1984).

The individual active ingredient units are particularly preferablyproduced by solidification from liquid phase by generating drops bymeans of vibrating nozzles and by solidifying the drops which areformed, after they have stabilized, by drying or cooling in a suitablemedium (preferably gaseous or liquid). The suitable medium may be, forexample, cooled gas such as air or nitrogen. Processes of this type andcorresponding apparatuses are disclosed in DE 27 25 924, EP 0 467 221,WO99/33555 and WO00/24382. It is particularly preferred in thisconnection for the liquid phase flowing to the nozzle to be kept at aconstant temperature. The solidification preferably takes place byinstantaneous cooling in a suitable cooling medium. In prilling,moreover it is preferred for the liquid phase flowing to the nozzle, thevibrating nozzle and the drops formed by prilling to be kept at aconstant temperature until their spherical shape has stabilized, and forthe solidification of the drops after their stabilization to be carriedout instantaneously by cooling with a gaseous or liquid cooling medium.Systems suitable for prilling by means of vibrating nozzles aremarketed, for example, by Brace GmbH, Alzenau, Germany. It is possibleby means of prilling using vibrating nozzles to obtain the individualactive ingredient units in the form of microspheres with a narrowmonomodal particle size spectrum in the particle size range from 50 μmto 2 mm. The narrow monomodal particle size spectrum and the uniformspherical shape of the microspheres obtained in this way are expected toresult in a uniformly smooth surface, a uniform, defined delivery ofactive ingredient and, in relation to passage through the stomach in thecase of oral dosage forms (owing to the small particles), a behaviorlike that of a solution. The microspheres of the invention distinguishedin particular by high stability, a release of active ingredient whichcan be controlled via the particle size and composition of the matrix,good flow characteristics, good compressibility and a uniform deliveryof active ingredient. It is particularly worthy of mention that themicrospheres can be further processed to a large number ofpharmaceutical dosage forms without thereby losing a given functionality(such as taste masking, resistance to gastric juice, slowing ofrelease). Thus, for example, on compression of the microspheres of theinvention to the rapidly disintegrating tablet of the invention there isobserved to be no loss of functionality, in particular of acidresistance. Compression of pellets with an enteric coating to tabletsmay on the other hand, as described at the outset, be difficult becausethere is always the risk that the compression is associated with damageto the coating and thus to the functionality, thus leading to anunwanted release or decomposition of the active ingredient.

The microspheres are preferably monomodal microspheres with a particlesize range of 50–800 μm, preferably 50–500 μm, particularly preferably50–400 μm, in particular 50–200 μm. The microspheres preferably comprisean acid-labile proton pump inhibitor.

The particle size of the active ingredient employed in the spray dryingor spray solidification, prilling or vibration prilling isadvantageously less than or equal to 100 μm, in particular less than 40μm. The particle size is preferably in the range 1–20 μm, particularlypreferably in the range 3–15 μm. Such a particle size can be achieved,for example, by grinding the active ingredient in a suitable mill.

The individual active ingredient units (preparations) of the inventioncan then be further processed together with excipients which bring aboutrapid disintegration of the tablet on oral intake to give the dosageform of the invention. Suitable excipients are, in particular, thoseexcipients which on oral intake of the tablet bring about rapiddisintegration of the tablet. Excipients which on oral intake of thetablet bring about rapid disintegration of the tablet preferablycomprise one or more substances selected from the group of fillers anddisintegrants. One or more other excipients from the group oflubricants, flavors, flavoring substances and surface-active substancesare preferably present in the rapidly disintegrating dosage form of theinvention. Binders can also be present if desired. The rapidlydisintegrating dosage form particularly preferably comprises a mixtureof at least one filler, one disintegrant and one lubricant. Fillerssuitable according to the invention are, in particular, basic fillerssuch as calcium carbonate (e.g. MagGran® CC or Destab® 95) and sodiumcarbonate, sugar alcohols such as mannitol (e.g. Perlitol® or Parteck®M), sorbitol (e.g. Karion®), xylitol or maltitol, starches such as cornstarch, potato starch and wheat starch, microcrystalline cellulose,saccharides such as glucose, lactose, levulose, sucrose and dextrose. Ina preferred embodiment of the invention the rapidly disintegratingdosage form comprises a basic filler such as sodium carbonate or calciumcarbonate. In a further preferred development of the invention, therapidly disintegrating dosage form of the invention comprises as fillera mixture of a basic filler (in particular calcium carbonate) and asugar alcohol (in particular sorbitol or mannitol). Disintegrantssuitable according to the invention are, in particular, insolublepolyvinylpyrrolidone (insoluble PVP, crospovidone), sodiumcarboxy-methylstarch, sodium carboxymethylcellulose, alginic acid andstarches able to carry out the function of a disintegrant (e.g. Starch1500). Suitable lubricants which may be mentioned are sodium stearylfumarate, magnesium stearate, calcium stearate, stearic acid, talc andhighly disperse silica (Aerosil). Suitable surface-active substanceswhich may be mentioned are sodium lauryl sulfate or Tween® 20, 60 or 80.Binders suitable according to the invention are polyvinylpyrrolidone(PVP, Polyvidon® K25, 90) or mixtures of PVP with polyvinyl acetate(e.g. Kollidon® 64), gelatin, cornstarch mucilage, preswollen starches(Starch 1500), hydroxypropylmethylcellulose (HPMC) orhydroxypropylcellulose (L-HPC).

In another embodiment of the invention the rapidly disintegrating tabletcontains one or more basic (alkaline) additives in particular additiveswhich are known to have antacid activity in the treatment ofgastrointestinal disorders associated with excess gastric acidexcretion. Examples of such basic additives having antacid activitywhich may be mentioned in connection with the invention are alkalinebuffer compounds such as trisodium phosphate, disodium phosphate,phosphates such as aluminium phosphate, hydroxides such as magnesiumhydroxide, aluminium hydroxide, aluminium-sodium-carbonate-dihydroxide,oxides, such as aluminium oxide or magnesium oxide, carbonates such assodium carbonate, magnesium carbonate, calcium carbonate, potassiumcarbonate, hydrogen carbonates such as sodium hydrogen carbonate,potassium hydrogen carbonate, alkaline amino acids or alkaline salts ofamino acids such as sodium glycine or suitable salts of fatty acids suchas potassium oleate, ammonium oleate or salts of bismuth such asalkaline bismuth nitrate, bismuth gallate, or silicats such asaluminium-magnesium-silicate, magnesiumtrisilicate, or magaldrate ormeglumine (USP 24) or trometamol (Ph.Eur.) or hydrotalcite. In apreferred embodiment of the invention the basic additive is a basicfiller. For rapidly disintegrating tablets according to the inventionwhich contain one or more basic (alkaline) additives with antacidactivity surprisingly a rapid onset of action and a shortening ofduration of treatment is observed in the treatment of gastrointestinaldisorders associated with excess acid excretion.

The proportion (in percent by weight based on the finished tablet) offiller in the rapidly disintegrating tablet is advantageously from 1 to99% by weight. The proportion of filler is preferably from 30 to 95% byweight, and the proportion is very particularly preferably from 60 to85% by weight.

The proportion (in percent by weight based on the finished tablet) ofdisintegrant in the rapidly disintegrating tablet is usually from 1 to30% by weight. The proportion of disintegrant is preferably from 2 to15% by weight. The proportion of disintegrant is particularly preferablyfrom 5 to 10% by weight.

The proportion (in percent by weight based on the finished tablet) oflubricant in the rapidly disintegrating tablet is usually from 0.1 to 5%by weight. The proportion of lubricant is preferably from 0.3 to 3% byweight. The proportion of lubricant is particularly preferably from 0.5to 2% by weight.

The proportion (in percent by weight based on the finished tablet) ofindividual active ingredient units in the rapidly disintegrating tabletis usually from 1 to 90% by weight. The proportion of individual activeingredient units is preferably up to 70% by weight, in particular from10 to 50% by weight. The proportion is very particularly preferably from15 to 25% by weight.

The proportion (in percent by weight based on the finished tablet) ofbinder can be up to 10% by weight, and it can preferably be up to 5% byweight.

Preferably the basic additive is present in an amount sufficient tocause a rapid onset of action in the treatment of gastrointestinaldisorders associated with excess gastric acid excretion. The proportion(in percent by weight based on the finished tablet) of basic additive ispreferably from 0.5 to 80% by weight. It is particularly preferred thatthe amount of basic additive in the rapidly disintegrating tablet isfrom 3 to 30% by weight.

If desired, one or more flavoring substances (e.g. flavors orsweeteners) can additionally be present in the rapidly disintegratingtablet. This makes it possible, for example, to achieve an improvementof the taste of the rapidly disintegrating tablet. These substances areadded in conventional amounts.

The rapidly disintegrating tablet is produced by processes known to theskilled worker. The rapidly disintegrating tablet is preferably producedby

-   -   i) dry mixing of filler and/or disintegrant;    -   ii) production of granules of filler and binder and mixing of        the granules with a disintegrant or    -   iii) dry granulation (briqueting or compacting) of one or more        excipient components.

The individual active ingredient units are subsequently admixed to themixtures obtained in i), ii) or iii) and then, if desired,flavors/flavoring substances and finally also one or more lubricants areadmixed. The mixture obtained in this way can be compressed in a tabletpress under conventional conditions.

Rapid disintegration of the tablet means according to the inventiondisintegration of the tablet in about 60 seconds or less when the tabletis subjected to a disintegration test as described in the EuropeanPharmacopoeia (3rd edition, 1997) 2.9.1 disintegration time of tabletsand capsules.

The rapidly disintegrating tablets of the invention comprise theacid-labile active ingredient in the dose customary for the treatment ofthe particular disorder. The acid-labile proton pump inhibitors of theinvention can be employed for the treatment and prevention of alldisorders which are regarded as treatable or preventable by the use ofpyridin-2-ylmethylsulfinyl-1H-benzimidazoles. In particular, the rapidlydisintegrating tablets of the invention can be employed for thetreatment of gastric disorders. Such rapidly disintegrating tabletscontain between 1 and 500 mg, preferably between 5 and 60 mg, of anacid-labile proton pump inhibitor. Examples which may be mentioned aretablets which contain 10, 20, 40 or 50 mg of pantoprazole. The dailydose (e.g. 40 mg of active ingredient) can be administered, for example,in the form of a single dose or by means of a plurality of doses of thetablets of the invention (e.g. 2×20 mg of active ingredient).

The tablets of the invention can be combined with other medicaments,either in different combinations or in a fixed combination. Combinationsworthy of mention in connection with the dosage forms of the inventionwhich comprise acid-labile proton pump inhibitors as active ingredientsare those with anti-microbial active ingredients and combinations withNSAIDs (nonsteroidal anti-inflammatory drugs). Particular mention shouldbe made of the combination with antimicrobial agents like those employedfor controlling the microbe Helicobacter pylori (H. pylori).

Examples of suitable antimicrobial active ingredients (active againstHelicobacter pylori) are described In EP-A-0 282 131. Examples ofantimicrobial agents which are suitable for controlling the microbeHelicobacter pylori and may be mentioned by way of example are bismuthsalts [e.g. bismuth subcitrate, bismuth subsalicylate, ammoniumbismuth(III) potassium citrate dihydroxide, bismuth nitrate oxide,dibismuth tris(tetraoxodialuminate)], but especially β-lactamantibiotics, for example penicillins (such as benzylpenicillin,phenoxymethylpenicillin, propicillin, azidocillin, dicloxacillin,flucloxacillin, oxacillin, amoxicillin, bacampicillin, ampicillin,mezlocllin, piperacillin or aziocillin), cephalosporins (such ascefadroxil, cefaclor, cefalexin, cefixime, cefuroxime, cefetamet,ceftibuten, cefpodoxime, cefotetan, cefazoline, cefoperazone,ceftizoxime, cefotaxime, ceftazidime, cefamandole, cefepime, cefoxitin,cefodizime, cefsulodin, ceftriaxone, cefotiam or cefmenoxime) or otherβ-lactam antibiotics (e.g. aztreonam, loracarbef or meropenem); enzymeinhibitors, for example sulbactam; tetracyclines, for exampletetracycline, oxytetracycline, minocycline or doxycycline;aminoglycosides, for example tobramycin, gentamicin, neomycin,streptomycin, amikacin, netilmicin, paromomycin or spectinomycin;amphenicols, for example chloramphenicol or thiamphenicol; lincomycinsand macrolide antibiotics, for example clindamycin, lincomycin,erythromycin, clarithromycin, spiramycin, roxithromycin or azithromycin;polypeptide antibiotics, for example colistin, polymixin B, teicoplaninor vancomycin; gyrase inhibitors, for example norfloxacin, cinoxacin,ciprofloxacin, pipemidic acid, enoxacin, nalidixic acid, pefloxacin,fleroxacin or ofloxacin; nitroimidazoles, for example metronidazole; orother antibiotics, for example fosfomycin or fusidic acid. Particularlyworthy of mention in this connection is the administration of anacid-labile proton pump inhibitor together with the combination of aplurality of antimicrobial active ingredients, for example with thecombination of a bismuth salt and/or tetracycline with metronidazole orthe combination of amoxicillin or clarithromycin with metronidazole andamoxicillin with clarithromycin.

The production of tablets and preparations of the invention is describedby way of example hereinafter. The following examples explain theinvention in detail without restricting it.

EXAMPLES Production of the Active Ingredient Units Example 1

50 g of solid paraffin, 34.9 g of cetyl alcohol and 0.1 g ofstearylamine are converted into a clear melt. 5.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 10.0 gof pantoprazole sodium sesquihydrate is added and suspendedhomogeneously. The suspension is prilled in the molten state, and thedrops thus produced are solidified in a cooling zone.

Example 2

55 g of solid paraffin, 30.9 g of cetyl alcohol and 0.1 g ofstearylamine are converted into a clear melt. 4.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 10.0 gof pantoprazole magnesium is added and suspended homogeneously. Thesuspension is prilled in the molten state, and the drops thus producedare solidified in a cooling zone.

Example 3

45.0 g of solid paraffin, 33.8 g of cetyl alcohol, 1.0 g of β-sitosteroland 0.2 g of stearylamine are converted into a clear melt. 1.0 g ofpovidone and 4.0 g of ethylcellulose are dissolved in the clear melt. Ata temperature between 56–60° C., 15.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state, and the drops thus produced are solidifiedin a cooling zone.

Example 4

52.0 g of solid paraffin, 30.3 g of cetyl alcohol and 0.2 g ofstearylamine are converted into a clear melt. 5.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 12.5 gof pantoprazole sodium sesquihydrate is added and suspendedhomogeneously. The suspension is prilled in the molten state, and thedrops thus produced are solidified in a cooling zone.

Example 5

77.2 g of cetyl alcohol and 0.3 g of stearylamine are converted into aclear melt. 10.0 g of povidone is dissolved in the clear melt. At atemperature between 56–60° C., 12.5 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state, and the drops thus produced are solidifiedin a cooling zone.

Example 6

47 g of solid paraffin, 40 g of glyceryltripalmitate (Dynasan 116, fromHüls) and 3 g of sitosterol are converted into a clear melt at 100° C.and cooled to 55–60° C. 10 g of lansoprazole are added and suspendedhomogeneously. The suspension is put in the feed container of a prillingunit (from Brace) and prilled from a 200 μm nozzle at about 0.1 bar. Aperiodic vibration with a frequency of about 390 Hz is transmitted tothe nozzle head during this. The resulting drops are solidified in acooling zone with air at a temperature of −30° C.

Example 7

15 g of glyceryl trimyristate (Dynasan 114), 15 grams of glyceryltripalmitate (Dynasan 116), 50 grams of solid paraffin and 5 g ofcholesterol are converted into a clear melt at about 100° C. The clearmelt is cooled to about 55–65° C. 15 g of rabeprazole are added, theactive ingredient is uniformly dispersed, and the homogeneous suspensionis prilled as in example 6.

Example 8

10 g of glyceryl tripalmitate (Dynasan 116), 20 g of glyceryltrimyristate (Dynasan 114), 52 g of solid paraffin and 3 g of sitosterolare converted into a clear melt at about 100° C. The clear melt iscooled to 55–65° C. 15 g of omeprazole Mg are added and suspendedhomogeneously. The suspension is put in the feed container of a prillingunit (from Brace) and prilled through a 200 μm nozzle at 90 mbar. Aperiodic vibration with a frequency of about 400 Hz is transmitted tothe nozzle head during this. The resulting drops are solidified with airat a temperature of −30° C. in a cooling zone.

Example 9

18 g of tristearin, 60 g of solid paraffin and 5 g of cholesterol areconverted into a clear melt. The clear melt is cooled to 56–60° C. 10 gof pantoprazole sodium sesquihydrate are introduced and homogeneouslydispersed. The suspension is prilled in the molten state in a prillingunit (from Brace) with vibrating nozzles, and the resulting drops aresolidified in a cooling zone.

Example 10

18 g of cetyl palmitate, 40 g of solid paraffin and 2 g of cholesterolare converted into a clear melt. The clear melt is cooled to 56–60° C.10 g of pantoprazole sodium sesquihydrate are introduced and homogenizeduntil a uniform suspension results. The suspension is prilled in themolten state in a prilling unit (from Brace) with vibrating nozzles, andthe resulting drops are solidified in a cooling zone.

Example 11

50 g of solid paraffin and 40 g of cetyl palmitate (Cutina® CP) areconverted into a clear melt at 100° C. The clear melt is cooled to50–60° C. 10 g of pantoprazole sodium sesquihydrate are introduced andsuspended homogeneously. The suspension is prilled in the molten statein a prilling unit (from Brace) with vibrating nozzles (200 μm nozzle),and the resulting drops are solidified in a cooling zone.

Example 12

50 g of solid paraffin and 40 g of cetyl alcohol are converted into aclear melt at 100° C. The clear melt is cooled to 50–60° C. 10 g ofpantoprazole sodium sesquihydrate are introduced and suspendedhomogeneously. The suspension is prilled in the molten state in aprilling unit (from Brace) with vibrating nozzles (200 μm nozzle), andthe resulting drops are solidified in a cooling zone.

Example 13

50 g of solid paraffin and 40 g of glyceryl trimyristate are convertedinto a clear melt at 100° C. The clear melt is cooled to 50–60° C. 10 gof pantoprazole sodium sesquihydrate are introduced and suspendedhomogeneously. The suspension is prilled in the molten state in aprilling unit (from Brace) with vibrating nozzles (200 μm nozzle), andthe resulting drops are solidified in a cooling zone.

Example 14

47 g of solid paraffin, 40 g of glyceryl tripalmitate (Dynasan 116, fromHüls) and 3 g of sitosterol are converted into a clear melt at 100° C.and cooled to 50–60° C. 10 g of lansoprazole are added and suspendedhomogeneously. The suspension is put into the feed container of aprilling unit (from Brace) and prilled from a 200 μm nozzle at about 0.1bar. A periodic vibration with a frequency of about 390 Hz istransmitted to the nozzle head during this. The resulting drops aresolidified in a cooling zone with air at a temperature of −30° C.

Example 15

30 g of tristearin, 60 g of solid paraffin and 4 g of sitosterol and0.07 g stearylamine are converted into a clear melt. The clear melt iscooled to 56–60° C., 15 g of pantoprazole sodium sesquihydrate areintroduced and homogeneously dispersed. The suspension is prilled in themolten state in a prilling unit (from Brace) with vibrating nozzles, andthe resulting drops are solidified in a cooling zone.

Example 16

17.5 g of glyceryl trimyristate (Dynasan 114), 67.5 g of solid paraffinand 5 g of cholesterol are converted into a clear melt at about 100° C.The clear melt is cooled to about 55–65° C. 10 g of pantoprazole areadded, and the active ingredient is uniformly dispersed, and thehomogeneous suspension is prilled as in example 6.

Example 17

56.7 g of cetyl alcohol, 3 g of vinylpyrollidone/vinyl acetatecopolymer, 15 g of solid paraffin, 15 g of cetyl palmitate and 0.1 g ofsodium stearate are converted into a clear melt. At a temperaturebetween 56–60° C., 10.0 g of pantoprazole sodium sesquihydrate is addedand suspended homogeneously. The suspension is prilled in the moltenstate at 60° C. and the drops thus produced are solidified in a coolingzone.

Example 18

46.7 g of cetostearylic alcohol, 4 g of vinylpyrollidone/vinyl acetatecopolymer, 23 g solid paraffin, 0.3 g of sodium stearate and 1 gsitosterol are converted into a clear melt. At a temperature between60–65° C., 10.0 g of pantoprazole sodium sesquihydrate is added andsuspended homogeneously. The suspension is prilled in the molten stateat 60 to 65° C. and the drops thus produced are solidified in a coolingzone.

Example 19

39.9 g of cetyl alcohol, 3 g of vinylpyrollidone/vinyl acetatecopolymer, 20 g of cetyl palmitate, 2 g cholesterol, 17 g solid paraffinand 0.1 g of sodium stearate are converted into a clear melt. At atemperature between 56–60° C., 18.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state at 60° C. and the drops thus produced aresolidified in a cooling zone.

Example 20

47.9 g cetostearylic alcohol, 2 g of vinylpyrollidone/vinyl acetatecopolymer, 25 g of cetyl palmitate, 1 g sitosterol, 15 g solid paraffinand 0.1 g of sodium stearate are converted into a clear melt. At atemperature between 56–60° C., 15.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state at 60° C. and the drops thus produced aresolidified in a cooling zone.

The preparations obtained as in examples 1–20 have a particle size inthe range 50–700 μm. It is possible, for example by varying the processconditions, to obtain larger particles.

Production of Rapidly Disintegrating Tablets Example A

1. MagGran ® CC 1008.0 mg 2. Karion ® 432.0 mg 3. Crospovidone 136.0 mg4. Preparation from example 1 400.0 mg 5. Magnesium stearate 24.0 mgTotal 2000.0 mg

Production: 1.–4. are mixed in a free-fall mixer. Then 5. is addedthrough a suitable sieve to the mixture of 1.–4., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example B

1. Destab ® 95 SE 1060.8 mg 2. Pearlitol ® 300 DC 387.2 mg 3.Crospovidone 136.0 mg 4. Preparation from example 16 400.0 mg 5.Magnesium stearate 16.0 mg Total 2000.0 mg

Production: 1.–4. are mixed in a free-fall mixer. Then 5. is addedthrough a suitable sieve to the mixture of 1.–4., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example C

1. Destab ® 95 SE 1072.0 mg 2. Pearlitol ® 300 DC 432.0 mg 3.Crospovidone 80.0 mg 4. Preparation from example 3 400.0 mg 5. Magnesiumstearate 16.0 mg Total 2000.0 mg

Production: 1.–4. are mixed in a free-fall mixer. Then 5. is addedthrough a suitable sieve to the mixture of 1.–4., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example D

1. MagGran ® CC 1008.0 mg 2. Karion ® 432.0 mg 3. Sodiumcarboxymethylcellulose 136.0 mg 4. Preparation from example 8 266.6 mg5. Magnesium stearate 24.0 mg Total 1866.6 mg

Production: 1.–4. are mixed in a free-fall mixer. Then 5. is addedthrough a suitable sieve to the mixture of 1.–4., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example E

1. Lactose 1-hydrate 1136.0 mg 2. Corn starch 288.0 mg 3. Polyvidon ® K25 80.0 mg 4. Sodium carboxymethylstarch 80.0 mg 5. Preparation fromexample 2 400.0 mg 6. Magnesium stearate 16.0 mg Total 2000.0 mg

Production: 1. and 2. are granulated with a solution of 3. Drying andscreening are carried out. 4. and 5. are admixed by means of a free fallmixer for several minutes, and then 6. is briefly admixed by means of afree fall mixer. The mixture obtained in this way is compressed in atablet press.

Example F

1. Lactose 1-hydrate 1136.0 mg 2. Corn starch 288.0 mg 3. Polyvidon ® K25 80.0 mg 4. Sodium carboxymethylcellulose 80.0 mg 5. Preparation fromexample 16 400.0 mg 6. Magnesium stearate 16.0 mg Total 2000.0 mg

Production: 1. and 2. are granulated with a solution of 3. Drying andscreening are carried out. 4. and 5. are admixed by means of a free fallmixer for several minutes, and then 6. is briefly admixed by means of afree fall mixer. The mixture obtained in this way is compressed in atablet press.

Example G

1. Lactose 1-hydrate 1192.0 mg 2. Corn starch 288.0 mg 3. Polyvidon ® K90 24.0 mg 4. Crospovidone 80.0 mg 5. Preparation from example 1 400.0mg 6. Magnesium stearate 16.0 mg Total 2000.0 mg

Production: 1. and 2. are granulated with a solution of 3. Drying andscreening are carried out. 4. and 5. are admixed by means of a free fallmixer for several minutes, and then 6. is briefly admixed by means of afree fall mixer. The mixture obtained in this way is compressed in atablet press.

Example H

1. MagGran ® CC 1008.0 mg 2. Karion ® 432.0 mg 3. Crospovidone 136.0 mg4. Preparation from example 1 400.0 mg 5. Microcrystalline cellulose400.0 mg 6. Magnesium stearate 24.0 mg Total 2400.0 mg

Production: 1.–5. are mixed in a free-fall mixer. Then 6. is addedthrough a suitable sieve to the mixture of 1.–5., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example I

1. Destab ® 95 SE 1060.8 mg 2. Pearlitol ® 300 DC 387.2 mg 3.Crospovidone 136.0 mg 4. Preparation from example 16 400.0 mg 5.Microcrystalline cellulose 400.0 mg 6. Magnesium stearate 16.0 mg Total2400.0 mg

Production: 1.–5. are mixed in a free-fall mixer. Then 6. is addedthrough a suitable sieve to the mixture of 1.–5., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example J

1. Destab ® 95 SE 1072.0 mg 2. Pearlitol ® 300 DC 432.0 mg 3.Crospovidone 80.0 mg 4. Preparation from example 3 400.0 mg 5.Microcrystalline cellulose 400.0 mg 6. Magnesium stearate 16.0 mg Total2400.0 mg

Production: 1.–5. are mixed in a free-fall mixer. Then 6. is addedthrough a suitable sieve to the mixture of 1.–5., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example K

1. MagGran ® CC 1008.0 mg 2. Karion ® 432.0 mg 3. Sodiumcarboxymethylcellulose 136.0 mg 4. Preparation from example 8 266.6 mg5. Microcrystalline cellulose 266.6 mg 6. Magnesium stearate 24.0 mgTotal 2133.2 mg

Production: 1.–5. are mixed in a free-fall mixer. Then 6. is addedthrough a suitable sieve to the mixture of 1.–5., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example L

1. sodium carbonate anhydrous 120.0 mg 2. Microcrystalline cellulose1360.0 mg 3. Sodium carboxymethylstarch 100.0 mg 4. Preparation fromexample 18 400.0 mg 5. Magnesium stearate 20.0 mg Total 2000.0 mg

Production: 1.–4. are mixed in a free-fall mixer. Then 5. is addedthrough a suitable sieve to the mixture of 1.–4., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example M

1. Microcrystalline cellulose 1480.0 mg 2. Sodium carboxymethylstarch100.0 mg 3. Preparation from example 19 400.0 mg 4. Magnesium stearate20.0 mg Total 2000.0 mg

Production: 1.–3. are mixed in a free-fall mixer. Then 4. is addedthrough a suitable sieve to the mixture of 1.–3., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example N

1. Microcrystalline cellulose 1480.0 mg 2. Preparation from example 20400.0 mg 3. Magnesium stearate 20.0 mg Total 1900.0 mg

Production: 1. and 2. are mixed in a free-fall mixer. Then 3. is addedthrough a suitable sieve to the mixture of 1.–2., followed by a briefmixing once again. The mixture obtained in this way is compressed in atablet press.

Example O

1. sodium carbonate anhydrous 60.0 mg 2. Microcrystalline cellulose1340.0 mg 3. Sodium carboxymethylstarch 50.0 mg 4. Polyvidon ® K 25 80.0mg 5. Preparation from example 17 400.0 mg 6. Sodium carboxymethylstarch50.0 mg 7. Magnesium stearate 20.0 mg Total 2000.0 mg

Production: 1., 2. and 3. are granulated with a solution of 4. Dryingand screening are carried out. 5. and 6. are admixed by means of a freefall mixer for several minutes, and then 7. is briefly admixed by meansof a free fall mixer. The mixture obtained in this way is compressed ina tablet press.

Example P

1. Microcrystalline cellulose 1330.0 mg 3. Sodium carboxymethylstarch150.0 mg 4. HPMC 2910 80.0 mg 5. Preparation from example 1 400.0 mg 6.Sodium carboxymethylstarch 50.0 mg 7. Magnesium stearate 20.0 mg Total2000.0 mg

Production: 1. and 2. are granulated with a solution of 3. Drying andscreening are carried out. 4. and 5. are admixed by means of a free fallmixer for several minutes, and then 6. is briefly admixed by means of afree fall mixer. The mixture obtained in this way is compressed in atablet press.

1. A rapidly disintegrating tablet for oral administration of anacid-labile active ingredient comprising a plurality of individualactive ingredient units together with one or more pharmaceuticalexcipients, where the acid-labile active ingredient is present in theindividual active ingredient units in a matrix composed of a mixturecomprising at least one solid paraffin and one or more substances fromthe group of fatty alcohol, triglyceride and fatty acid ester, and whereexcipients which, on oral intake of the tablet, bring about rapiddisintegration of the tablet are present, wherein said acid-labileactive ingredient is a proton pump inhibitor, or a hydrate, solvate,salt, hydrate of a salt or solvate of a salt thereof.
 2. A rapidlydisintegrating tablet for oral administration of an acid-labile activeingredient comprising a plurality of individual active ingredient unitstogether with one or more pharmaceutical excipients, where theacid-labile active ingredient is present in the individual activeingredient units i) in a matrix composed of a mixture comprising atleast one fatty alcohol and at least one solid paraffin, ii) in a matrixcomposed of a mixture comprising at least one triglyceride and at leastone solid paraffin or iii) in a matrix composed of a mixture comprisingat least one fatty acid ester and at least one solid paraffir, and whereexcipients which, on oral intake of the tablet, bring about rapiddisintegration of the tablet are present, wherein said acid-labileactive ingredient is a proton pump inhibitor, or a hydrate, solvate,salt, hydrate of a salt or solvate of a salt thereof, and wherein thetablet disintegrates in about 60 seconds or less when the tablet issubjected to a disintegration test as described in EuropeanPharmacopoeia, 3^(rd) Edition, 1997, 2.9.1 disintegration time oftablets and capsules.
 3. A tablet as claimed in claim 1, where theexcipients which bring about rapid disintegration of the tablet compriseone or more substances selected from the group consisting of fillers anddisintegrants.
 4. A tablet as claimed in claim 3, where the fillercomprises a mixture of a sugar alcohol and a basic filler.
 5. A tabletas claimed in claim 3, where the excipients comprise a mixture of atleast one filler, one disintegrant and one lubricant.
 6. A tablet asclaimed in claim 3, where one or more excipients selected from the groupconsisting of lubricants, flavors, flavoring substances andsurface-active substances are additionally present.
 7. A tablet asclaimed in claim 1, wherein the individual active ingredient units aremicrospheres.
 8. A tablet as claimed in claim 1, wherein the acid-labileactive ingredient is selected from the group consisting of pantoprazole,a hydrate of pantoprazole, a solvate of pantoprazole, a salt ofpantoprazole, a hydrate of a salt of pantoprazole or a solvate of a saltof pantoprazole.
 9. A tablet as claimed in claim 1, which comprises abasic filler.
 10. A tablet as claimed in claim 2, wherein the individualactive ingredient units are microspheres.
 11. A tablet as claimed inclaim 4, wherein the basic filler is calcium carbonate.
 12. A tablet asclaimed in claim 2, wherein the acid-labile active ingredient isselected from the group consisting of pantoprazole, a hydrate ofpantoprazole, a solvate of pantoprazole, a salt of pantoprazole, ahydrate of a salt of pantoprazole or a solvate of a salt ofpantoprazole.
 13. A tablet as claimed in claim 1, wherein theacid-labile active ingredient is selected from the group consisting ofpantoprazole sodium sesquihydrate, (−)-pantoprazole magnesium dihydrate,omeprazole magnesium, omeprazole and esomeprazole.
 14. A tablet asclaimed in claim 2, wherein the acid-labile active ingredient isselected from the group consisting of pantoprazole sodium sesquihydrate,(−)-pantoprazole magnesium dihydrate, omeprazole magnesium, omeprazoleand esomeprazole.